PB2206: PROGRESSION FACTORS OF MYELOFIBROSIS BASED ON CLINICAL FEATURES AND NEXT-GENERATION SEQUENCING LANDSCAPE OF ESSENTIAL THROMBOCYTHEMIA: A CHINES TWO-CENTER RETROSPECTIVE STUDY
Authors: Danhong Xiang, Shiwei Hu, Xinlu Zhang, Lan Zhang, Shengjie Wang, Qiutian Feng, Jian Huang
Journal: HemaSphere (2023)

Topic: 16. Myeloproliferative neoplasms - Clinical Background: Essential thrombocythemia (ET) was characterized by aberrant hematopoietic proliferation with the risk of myelofibrosis (MF) progression. Red blood cell distribution width (RDW) and ASXL1 as a chromatin modifier may be associated with MF progression. However, there is no report of their influences on the MF progression of ET patients. Aims: To analyze the prognostic factors of the MF progression of ET patients. Methods: We concluded a retrospective study of 354 ET patients from October 2014 to December 2022 in the Fourth Affiliated Hospital and the First Affiliated Hospital of Zhejiang University School of Medicine. Patients were divided into the non-myelofibrosis (non-MF) progression group and the myelofibrosis (MF) progression group. Patients with incomplete information from laboratory tests and medical records were excluded. This study was approved by the Ethics Committee of the Fourth Affiliated Hospital and the First Affiliated Hospital of Zhejiang University School of Medicine. Statistical analyses were performed using SPSS statistics 26.0 and GraphPad Prism 8.0 software. Results: In universal analyses, the MF progression group exhibited lower hemoglobin values [105 (92-116)g/L vs 130 (119~140)g/L, P<0.001], platelet values [676 (462-798)×10^9/L vs 791 (639-1028)×10^9/L, P=0.020], hematocrit values [39 (35-42)% vs 33 (31~36)%, P<0,001], and triglyceride values [1.45(1.15-1.75)mmol/L vs 1.2(0.85-1.67)mmol/L, P=0.011]. On the contrary, it showed higher RDW values [17.2(15.6-22.2)% vs 13.9(13.1-15.3)%, P<0.001], higher uric acid values [368(265-455)U/L vs 308(249-375) U/L, P=0.013], a higher proportion of splenomegaly [82.9% vs 14.4%, P<0.001], and a higher proportion of smoking [46.2% vs 6.7%, P<0.001]. In multiple analyses, RDW>15%[OR 12.899 95% CI(3.003-55.526), P=0.001], smoking[OR 6.540 95% CI (1.943-22.013), P=0.002], splenomegaly [OR 12.442 95% CI (3.698-41.863), P<0.001], higher LDH values[OR 1.005 95% CI (1.000=1.009), P=0.036], and lower platelet values[OR 0.996 95% CI (0.994-0.999), P=0.002] were still significantly different (Figure A). Additionally, next-generation sequencing landscape was performed in 40 ET patients, in which 13 MF progression patients had identified 47 mutations of 30 different types and 27 non-MF progression patients had identified 88 mutations of 49 different types. JAK2V617F and TET2 mutation were common in non-MF progression patients (Figure C) while the mutation of ASXL1 was ranked number two in MF progression patients (Figure B). The MF progression had a higher frequency of ASXL1 mutation than the non-MF progression (38.5% vs 3.7%) (Figure D), revealed the ASXL1 mutation was a risk factor to MF progression [OR 16.250 95% CI (1.648-160.243), P=0.017]. Conclusion: Higher RDW (>15%) was an independent prognostic factor for MF progression. ET patients with ASXL1 mutation were more likely to progress into MF. Acknowledgement: This research was funded by the Key R&D Program of Zhejiang, No. 2022C03137; Public Technology Application Research Program of Zhejiang, China, No. LGF21H080003; Zhejiang Medical Association Clinical Medical Research special fund project, No. 2022ZYC-D09; the Key Project of Jinhua Science and Technology Plan, China, No. 2020-3-011.*Correspondence to: Prof Jian Huang.Keywords: Essential Thrombocytemia